Critical limitations of prognostic signatures based on risk scores summarized from gene expression levels: a case study for resected stage I non-small-cell lung cancer
Critical limitations of prognostic signatures based on risk scores summarized from gene expression levels: a case study for resected stage I non-small-cell lung cancer
复制标题
基于从基因表达水平总结的风险评分的预后特征的关键局限性：切除的 I 期非小细胞肺癌的案例研究
DOI：
10.1093/bib/bbv064
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发表时间：
2016-03-01
影响因子：
9.5
通讯作者：
Guo, Zheng
中科院分区：
文献类型：
--
作者：
Qi, Lishuang;Chen, Libin;Guo, Zheng
目前大多数用于癌症预后的基因表达标记是基于风险评分的，通常计算为标记基因表达水平的一些汇总，其应用需要预先设定风险评分阈值和数据归一化。在这项研究中，我们证明了这种类型的签名的关键局限性，即当样本与不同样本一起归一化时，样本的风险评分会发生很大变化，这将导致虚假的风险分类和临床设置的困难，如果不采用数据归一化，独立样本的风险评分是不可比的。为了克服这些局限性，我们提出了一种基于秩的方法来提取I期非小细胞肺癌总生存率的预后基因对签名。在由不同实验室用不同微阵列平台检测的三个整合数据集中验证预后基因对签名。我们的结论是，不同于基于基因表达水平总结的风险评分的签名类型，基于等级的签名可以在个体化水平上稳健地应用于在不同实验室评估的独立临床样本。
Most of current gene expression signatures for cancer prognosis are based on risk scores, usually calculated as some summaries of expression levels of the signature genes, whose applications require presetting risk score thresholds and data normalization. In this study, we demonstrate the critical limitations of such type of signatures that the risk scores of samples will change greatly when they are normalized together with different samples, which would induce spurious risk classification and difficulty in clinical settings, and the risk scores of independent samples are incomparable if data normalization is not adopted. To overcome these limitations, we propose a rank-based method to extract a prognostic gene pair signature for overall survival of stage I non-small-cell lung cancer. The prognostic gene pair signature is verified in three integrated data sets detected by different laboratories with different microarray platforms. We conclude that, different from the type of signatures based on risk scores summarized from gene expression levels, the rank-based signatures could be robustly applied at the individualized level to independent clinical samples assessed in different laboratories.